Improved understanding of antimicrobial (poly)peptides in airways secrections and their interactions with each other and with the ionic components in the fluid will provide a framework for understanding the pathogenesis of cystic fibrosis (CF) and for developing corrective interventions. Most of the morbidity and mortality of CF is the result of progressive pulmonary damage due to uncontrolled inflammation in the airways. Persistent airway colonization by Pseudomonas aeruginosa and other bacteria is either a direct cause of the uncontrolled inflammation or at least the major exacerbating factor. Several studies correlate the high chloride concentration present in CF airways to the decrease in antimicrobial activity due to salt-related inhibition of a cationic antimicrobial peptide. Preliminary data by our group suggests that the airways' antimicrobial activity is due to the combined effects of multiple factors. This study will test the hypothesis that airways host defense is mediated in part by cationic antimicrobial peptides acting synergistically with larger antimicrobial proteins in airways secretions. Specifically, we will: 1) purify and identify cationic peptides and proteins from human nasal secretions; 2) characterize the functional interactions between cationic peptides and major proteins found in human nasal secretions; and, 3) identify possible factors that would interfere with cationic peptide antimicrobial function in the CF airway.